Prothoracicotropic hormone has an insulin‐like tertiary structure

FEBS Letters

Ishizaki, H.¹  McLeod, A.N.³  Jhoti, H.³  Blundell, T.L.³  Nagasawa, H.²  Suzuki, A.² 

[1] Faculty of Science, Nagoyal University, Chikusa, Nagoya 464 Japan;Department of Agricultural Chemistry, Faculty of Agriculture, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan;Laboratory of Molecular Biology, Department of Crystallography, Birkbeck College, London University, Malet Street, London WC1E 7HX, England

关键词: Prothoracicotrophic hormone;    Tertiary structure;    Sequence homology;    Structure modeling;    Evolution;   

DOI  :  10.1016/0014-5793(87)80264-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A three-dimensional model of PTTH-II has been constructed using interactive computer graphics and energy minimisation techniques, assuming homology with porcine insulin, the structure of which has been determined by X-ray analysis. The model shows that PTTH-II can assume an insulin-like tertiary structure, which is compact with the exception of the sequence variable NH₂-terminal amino acids of the B chain. Most of the hydrophobic core residues including A2 Ile, A6 Cys, A11 Cys, A16 Leu, A20 Cys, B11 Leu, B15 Leu and B19 Cys are identical in PTTH-II and insulins. The glycines at A1, B8 and B23 allow the chain to assume the characteristic tertiary interactions of the insulin fold and although polypeptide chains are shorter at the COOH-termini of the A and B chains and extended at the NH₂-terminus of the B chain, the insulin-like tertiary structure can still be assumed. It is unlikely that PTTH-II forms either dimers or hexamers, characteristic of porcine and human insulin, and the model is consistent with the inability of PTTH-II to bind anti-insulin antibodies or insulin receptors. A hydrophobic surface region of PTTH-II may be involved in intermolecular actions of physiological relevance. We discuss the implications of our model for evolution of this family of hormones and growth factors.

【 授权许可】

Unknown